Brain-derived Neurotrophic Factors Val66Met and C270T Polymorphisms Influence Citalopram/Escitalopram Response in Chinese Patients with Major Depressive Disorder

Abstract

The aim of this study was to investigate the association between two brain-derived neurotrophic factor polymorphisms (Val66Met and C270T) and response to citalopram/escitalopram treatment. Chinese patients who met diagnostic and Statistical Manual of Mental Disorders criteria for major depressive disorder (n=180) were prescribed citalopram/escitalopram for 6 weeks. Depression severity was evaluated using the 17-item Hamilton rating scale for depression at baseline and week 2, 4, and 6 of treatment. The expression quantitative trait loci analysis was performed to investigate the functional effect of Val66Met and C270T on brain-derived neurotrophic factor expression in the brain and blood. A significant difference was found in genotype (χ2=6.979, p=0.031, correction p=0.062) but not allele (p>0.05) frequencies of Val66Met between responders and non-responders. Homozygous GG showed a higher response than other two genotypes (χ2=5.218, p=0.022, correction p=0.044). In addition, the C allele and CC genotype of C270T were significantly related to higher remission over 6 weeks among females (C/T, p=0.027, correction p=0.054; CC/TT, p=0.023, correction p=0.046) and first-episode major depressive disorder patients (C/T, p=0.023, correction p=0.046; CC/TT, χ2= 6.870, p=0.009, correction p=0.018). Further expression quantitative trait loci analysis showed that Val66Met and C270T have functional effect on brain-derived neurotrophic factor expression in the brain. Brain-derived neurotrophic factor Val66Met and C270T polymorphisms were associated with therapeutic response to citalopram/escitalopram in Chinese major depressive disorder patients.